Data suggest that patients infected with human immunodeficiency virus-1 (HIV) experience chronic lung inflammation, rapid lung function decline, and an increased risk of chronic obstructive pulmonary disease (COPD). Although potent combination antiretroviral treatment (ART) appears to reduce lung inflammation, the effects of ART on the rate of lung function decline and other important clinical outcomes remain unknown. This study is designed to address this knowledge gap, while providing a better understanding of the mechanisms for the rapid lung function decline observed in patients with HIV infection. This study has randomized 1,026 participants from 80 sites and 20 countries in a Pulmonary Substudy within a large, international, randomized, controlled trial - the Strategic Timing of AntiRetroviral Treatment (START) trial-and the study plans to follow these participants until unblinding in December 2016. The parent START trial has randomized 4,688 HIV-infected persons who were nave to antiretroviral treatment, with a CD4+ count >500 cells/mm3. Participants were randomized to either immediate initiation of potent ART or deferral of ART until the CD4+ count declines to <350 cells/mm3. Participants in the Pulmonary Substudy were enrolled prior to randomization, thus permitting an appropriately controlled experimental comparison of the effects of immediate vs. deferred ART treatment on pulmonary outcomes. START is the only ongoing multi-site randomized study comparing immediate vs. deferred ART, and the Pulmonary Substudy is among the few (and the largest) randomized intervention trials underway focused on HIV-associated lung disease. The extensive biological specimen repository, including genetic data and other data collected as part of the parent START protocol, will provide opportunities for multiple future investigations of biomarkers, genomics, metabolomics and other mechanistic work directed at understanding the development of COPD in patients infected with HIV. This study will advance understanding of the pathogenesis of rapid lung function decline and subsequent COPD in the presence of HIV infection.